Impact of induction approach on post-stem cell transplant (SCT) outcomes in older adults with newly diagnosed acute myeloid leukemia (AML).
Authors: Faustine Ong, Farhad Ravandi, Uday R. Popat, Tapan M. Kadia, Naval Guastad Daver, Courtney Denton Dinardo, Marina Konopleva, Gautam Borthakur, Elizabeth J. Shpall, Betul Oran, Gheath Alatrash, Rohtesh S. Mehta, Elias Jabbour, Musa Yilmaz, Ghayas C. Issa, Guillermo Garcia-Manero, Abhishek Maiti, Hussein Abbas, Richard E. Champlin, Nicholas James Short
Journal: Journal of Clinical Oncology (2022)

7038 Background: The optimal induction regimen for older patients (pts) with AML who are eligible for SCT is not well-established. Methods: This is a retrospective analysis of 127 pts age ≥60 years with newly diagnosed AML who underwent allogeneic SCT in first remission between 9/2012 and 7/2021 at our institution. Pts with previously treated secondary AML were excluded. Pts were divided according to induction therapy received: intensive chemotherapy (IC) (n = 44), lower-intensity therapy (LIT) without venetoclax (VEN) (n = 36), and LIT with VEN (n = 47). We compared overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) according to the induction regimen received. Results: Pts who received IC were younger than those who received LIT with or without VEN (median age: 63 vs. 68 years; P &lt; 0.0001) and were more likely to have an ECOG performance status of 0 at time of AML diagnosis (34% vs. 14%; P = 0.02). Cytomolecular risk was well-balanced between the 3 arms; the rates of adverse cytomolecular features in the IC, LIT without VEN and LIT with VEN groups were 43%, 50%, and 55%, respectively. Donor sources and degree of HLA matching were similar in the 3 groups. Most pts (92%) in the LIT with VEN group received reduced-intensity conditioning prior to SCT, compared with 54% and 58% in the IC and LIT without VEN groups, respectively. The majority of pts achieved CR/CRi prior to SCT (IC cohort:100%, LIT without VEN: 94%, LIT with VEN: 92%); the rest had MLFS as best response. The rate of measurable residual disease (MRD) negativity by flow cytometry prior to SCT was higher in the LIT with VEN group (69%), compared with IC (58%) and LIT without VEN (49%) (P = 0.14). The median number of cycles of chemotherapy prior to SCT was 3 in all groups. The median post-SCT follow-up was 37 months. The 2-year CIR was similar in pts who received IC or LIT with VEN (18% and 19%, respectively) and was highest in pts who received LIT without VEN (36%). The 2-year NRM was lowest in pts with LIT with VEN (11%), as compared with IC or LIT without VEN (27% and 22%, respectively) (P = 0.02 for IC vs. LIT with VEN). The 1-year post-SCT RFS for pts who received IC, LIT without VEN and LIT with VEN was 58%, 50%, and 75%, respectively, and the 2-year RFS was 54%, 42% and 62%. The 1-year post-SCT OS was 63%, 58%, and 84%, respectively, and the 2-year OS was 58%, 44% and 73%. OS was statistically superior for LIT with VEN compared with LIT without VEN (P = 0.02) and there was a trend towards superior OS with LIT with VEN compared to IC (P = 0.17). Conclusions: LIT with VEN was associated with similar rates of CIR and lower NRM compared with IC. Despite the older age of pts in the LIT with VEN cohort, their post-SCT survival outcomes were noninferior, and possibly superior, to those who received IC. These results suggest that LIT with VEN is a valid induction strategy for older SCT-eligible pts with newly diagnosed AML.